Counseling Points - March 2008 - (Page 8)

ment, often in combination with other modes of therapy.2,3 To reduce the incidence and severity of adverse events, short- or intermediate-acting compounds, such as prednisone and prednisolone, are preferred to long-acting agents, such as dexamethasone.2,3 The list of adverse reactions corticosteroids can promote is long and new problems with the medications are continually being encountered. Corticosteroids may cause water retention, elevated blood sugar, and suppression of adrenal glands and the immune system.2 The compounds also promote bone loss by blocking the absorption of calcium, inhibiting collagen synthesis, and increasing the excretion of calcium by the kidney.2 Corticosteroids may alter the immune response and, therefore, can increase susceptibility to bacterial, viral, and fungal infections.2 Other side effects of corticosteroids are cataracts, glaucoma, weight gain, osteoporosis, hypertension, and hyperlipidemia.2,3 Disease Modifying Anti-Rheumatic Drugs (DMARDs) In 2002, the American College of Rheumatology (ACR) established new guidelines for RA treatment.3 Goals of therapy now include an emphasis on targeting specific points of the disease pathway in order to obtain an optimal balance of efficacy, safety, and tolerability. The guidelines state that the first step in managing the effects of RA is to initiate DMARD therapy within the first 3 months of diagnosis.3 DMARDs are categorized into two subsets: traditional DMARDs and biologic DMARDs. There are a number of DMARDs currently available and each has a unique pharmacodynamic profile.18,19 Biologic DMARDs have novel mechanisms of action and more rapid onsets of action than conventional agents.18,19 The most commonly used traditional DMARDs are methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, while currently available biologic DMARDs include abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab. ate works is not completely understood, it is thought to be related to how the drug interrupts adenosine and diminishes cytokine production.21 Dosing begins at 10 mg to 15 mg per week with a dose escalation up to 25 mg per week. Methotrexate can be given orally or by injection and the usual time before a clinical benefit can be realized is 4 to 6 weeks.3,18,21 Side effects of methotrexate include nausea, oral ulcers, mild alopecia, and GI upset.18,21 Because the drug has folic acid antagonistic properties, oral folic acid supplements are generally prescribed at low daily doses.18,21 More serious side effects of methotrexate therapy include interstitial pneumonitis (“methotrexate lung”) and hepatic cirrhosis, and patients should be routinely monitored for elevated liver enzymes.18,21 Methotrexate has teratogenic properties. Women of childbearing potential or men who have partners of childbearing potential must practice effective birth control and should discontinue methotrexate for at least 3 months prior to attempting conception.18 Additionally, caution should be taken when using methotrexate with NSAIDs. Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and GI toxicity have been reported with concomitant administration of methotrexate (usually in high doses) along with some NSAIDs.22 Hydroxychloroquine (Plaquenil®) Hydroxychloroquine is an antimalarial drug that is a relatively safe and well-tolerated agent for the treatment of RA. Because its effectiveness is limited, the compound is sometimes combined with methotrexate for increased disease control or as part of a regimen of “triple therapy” with methotrexate and sulfasalazine. The mechanism of action of hydroxychloroquine is not completely understood, but the drug is thought to affect the immune system by interfering with antigen processing in macrophages and other antigen-presenting cells.23 Initially, hydroxychloroquine is dosed at 400 mg to 600 mg per day and continued until a good clinical response is obtained.19 The dose may then be reduced by 50% and continued daily at a usual maintenance dose of 200 mg to 400 mg. The length of time until treatment benefit occurs is generally 2 to 4 months and sometimes up to 6 months.19 Some experts maintain that if a response to hydroxychloroquine has not been demonstrated after 5 to 6 months, it should be considered a drug failure. Hydroxychloroquine is the most well-tolerated agent of 8 Traditional DMARDs Methotrexate (Rheumatrex®, Trexall®) Methotrexate is an antimetabolite drug and is considered first-line treatment for RA.20 Clinical studies have identified that half the patients who take methotrexate continue to take it beyond 3 years, which is longer than any other DMARD.3 Methotrexate is the standard by which new DMARDs are evaluated and can be used concomitantly with both traditional and biologic DMARDs. Although the mechanism of action by which methotrexCOUNSELING POINTS™

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Counseling Points - March 2008 Welcome Pharmacological and Nonpharmacological Treatment of Rheumatoid Arthritis

Counseling Points - March 2008

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